We already see this with legal marijuana, there are multiple campaigns aimed to form interstate compacts without the consent of congress. Ultimately a situation where the federal government declines to enforce its legal authority will just lead to a defacto change in the supremacy clause of the US constitution.
The only situation I see where this would become problematic is if a state chose to stop sending tax dollars to the federal government. Even then, the federal government has levers to pull that would be tough for a state to circumvent except by exiting the dollar - which no state has any reason to do.